著者

大野 雅恵

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.128, no.3, pp.343-355, 2008-03-01 (Released:2008-03-01)

参考文献数

62

被引用文献数

4 4

---

Nuclear receptors function as ligand-inducible transcription factors that regulate various physiological functions such as development, reproduction, and metabolism. Dysregulation of the metabolism of cholesterol, triglyceride, and glucose leads to the metabolic syndrome including type 2 diabetes mellitus, obesity, dyslipidemia, and atherosclerosis. Studies of nuclear receptors promise to provide discoveries of therapeutic agents against the metabolic syndrome. Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily and is activated by bile acids. FXR regulates the metabolism of not only bile acid but also cholesterol, lipoprotein, triglyceride, and glucose, and is considered a potential therapeutic target for the metabolic syndrome because of these functions. Nuclear receptors have two regions for transactivation, a constitutive activation function (AF-1) and a ligand-dependent activation function (AF-2). AF-1 and AF-2 seem to require interactions with coactivators for the activation function and both work synergistically to give full transactivation of nuclear receptors. However, coactivators for AF-1 activity are poorly understood, whereas coactivators required for AF-2 activity have been well studied. To understand the molecular mechanism of AF-1 in FXR, we isolated proteins associated with AF-1 by GST pull-down assay using the N-terminal region of FXR and nuclear extracts from HeLa cells. This review focuses on the roles of FXR and our new findings regarding FXR-associated factors.

著者

谷口 雄一 大野 雅恵

出版者

一般社団法人 日本生物物理学会

雑誌

生物物理 (ISSN:05824052)

巻号頁・発行日

vol.59, no.6, pp.305-309, 2019 (Released:2019-11-25)

参考文献数

14

---

The nucleosome arrangement in the genome is an important long-standing problem in biology. To address this, we recently developed a new technology for investigating 3D positions and orientations of nucleosomes across the genome. Analysis of the yeast genome revealed that the nucleosome arrangement is composed of two basic structures, named α-tetrahedron and β-rhombus. Further, we discovered that the nucleosome arrangement is distinct at every genomic locus depending on epigenetic regulation. The results provide the molecular basis of transcriptional and epigenetic events on the genome.